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https://www.readbyqxmd.com/read/28534531/unravelling-the-biology-of-sclc-implications-for-therapy
#1
REVIEW
Joshua K Sabari, Benjamin H Lok, James H Laird, John T Poirier, Charles M Rudin
Small-cell lung cancer (SCLC) is an aggressive malignancy associated with a poor prognosis. First-line treatment has remained unchanged for decades, and a paucity of effective treatment options exists for recurrent disease. Nonetheless, advances in our understanding of SCLC biology have led to the development of novel experimental therapies. Poly [ADP-ribose] polymerase (PARP) inhibitors have shown promise in preclinical models, and are under clinical investigation in combination with cytotoxic therapies and inhibitors of cell-cycle checkpoints...
May 23, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28534503/tumour-vessel-normalization-and-immune-checkpoint-blockade-a-new-synergism
#2
Ruth Ganss
No abstract text is available yet for this article.
May 23, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28534250/advancing-immunotherapy-in-metastatic-breast-cancer
#3
REVIEW
Mariam Mansour, Zhi Ling Teo, Stephen J Luen, Sherene Loi
Despite many advances in the treatment of breast cancer, the development of metastatic disease remains an incurable and frequent cause of cancer death for women worldwide. An improved understanding of the role of host immunosurveillance in modulating breast cancer disease biology, as well as impressive survival benefits seen to checkpoint blockade in other malignancies have provided great hope for an expanding role of immunotherapies in breast cancer management. While these novel therapies are currently being investigated in clinical trials, signals of efficacy, and tolerability in early phase studies suggest these will eventually make their way into standard practice algorithms...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28534248/immune-checkpoint-inhibitor-therapy-what-line-of-therapy-and-how-to-choose
#4
REVIEW
Chethan Ramamurthy, James L Godwin, Hossein Borghaei
Immunotherapy is now an established part of the treatment paradigm for advanced non-small cell lung cancer (NSCLC), but the line of therapy and the sequence of agents are still in flux. In this time when much is to be learned, the optimal therapy for most patients in both the first-line and previously treated settings is in the context of a clinical trial. For standard therapy, however, there are good data to support the practice of programmed death-ligand 1 (PD-L1) testing in the front-line advanced setting and to use pembrolizumab as first-line therapy for those with ≥50% PD-L1 expression...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28533658/checkpoint-inhibitors-in-gastrointestinal-cancers-expectations-and-reality
#5
EDITORIAL
Hampig Raphael Kourie, Samer Tabchi, Marwan Ghosn
Immune checkpoint inhibitors represent revolutionary anti-cancer agents, being rapidly approved in different malignancies and settings. Gastrointestinal (GI) cancers represent a wide variety of tumors with specific characteristics and different responses to various therapeutic alternatives; while some are chemo-sensitive others are chemo-resistant and only respond to more aggressive cytotoxic regimens, targeted therapies or a combination of both. Preliminary results of immune checkpoint inhibitors in some GI cancers are promising, namely in hepatocellular carcinoma, anal cancers and microsatellite instability high colorectal cancers...
May 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28533414/manipulating-dna-damage-response-signaling-for-the-treatment-of-immune-mediated-diseases
#6
Jonathan P McNally, Scott H Millen, Vandana Chaturvedi, Nora Lakes, Catherine E Terrell, Eileen E Elfers, Kaitlin R Carroll, Simon P Hogan, Paul R Andreassen, Julie Kanter, Carl E Allen, Michael M Henry, Jay N Greenberg, Stephan Ladisch, Michelle L Hermiston, Michael Joyce, David A Hildeman, Jonathan D Katz, Michael B Jordan
Antigen-activated lymphocytes undergo extraordinarily rapid cell division in the course of immune responses. We hypothesized that this unique aspect of lymphocyte biology leads to unusual genomic stress in recently antigen-activated lymphocytes and that targeted manipulation of DNA damage-response (DDR) signaling pathways would allow for selective therapeutic targeting of pathological T cells in disease contexts. Consistent with these hypotheses, we found that activated mouse and human T cells display a pronounced DDR in vitro and in vivo...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533272/chimeric-pd-1-28-receptor-upgrades-low-avidity-t-cells-and-restores-effector-function-of-tumor-infiltrating-lymphocytes-for-adoptive-cell-therapy
#7
Ramona Schlenker, Luis Felipe Olguín-Contreras, Matthias Leisegang, Julia Schnappinger, Anja Disovic, Svenja Rühland, Peter J Nelson, Heinrich Leonhardt, Hartmann Harz, Susanne Wilde, Dolores J Schendel, Wolfgang Uckert, Gerald Willimsky, Elfriede Noessner
Inherent intermediate-to-low affinity T cell receptors (TCR) that develop during the natural course of immune responses may not allow sufficient activation for tumor elimination, making the majority of T cells suboptimal for adoptive T cell therapy (ATT). TCR affinity enhancement has been implemented to provide stronger T cell activity but carries the risk of creating undesired cross-reactivity leading to potential serious adverse effects in clinical application. We demonstrate here that engineering of low-avidity T cells recognizing a naturally processed and presented tumor-associated antigen with a chimeric PD-1:28 receptor increases effector function to levels seen with high-avidity T cells of identical specificity...
May 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28531337/correlation-of-immune-phenotype-with-idh-mutation-in-diffuse-glioma
#8
Anna Sophie Berghoff, Barbara Kiesel, Georg Widhalm, Dorothee Wilhelm, Orsolya Rajky, Sebastian Kurscheid, Philip Kresl, Adelheid Wöhrer, Christine Marosi, Monika E Hegi, Matthias Preusser
Background: Tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) are targets of immune checkpoint inhibitors. Methods: Forty-three World Health Organization (WHO) grade II/III gliomas (39 IDH-mutant [mut], 4 IDH-wildtype [wt]) and 14 IDH-mut glioblastomas (GBM) were analyzed for TIL (CD3+; PD1+) infiltration and PD-L1 expression. Results were compared with the data of a previously published series of 117 IDH-wt glioblastomas. PD-L1 gene expression levels were evaluated in 677 diffuse gliomas grades II-IV from The Cancer Genome Atlas (TCGA) database...
May 20, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28529947/immune-checkpoint-blockade-for-hematologic-malignancies-a-review
#9
REVIEW
Matthew J Pianko, Yuzhou Liu, Srishti Bagchi, Alexander M Lesokhin
Immune checkpoint blockade has revolutionized the treatment of cancer, with impressive responses seen in a broad variety of tumor types. Blockade of immune checkpoints and immune signaling antibodies has shown promise in multiple types of hematologic malignancies (HMs), with dramatic single agent responses for pembrolizumab and nivolumab in Hodgkin lymphoma (HL). In this review, we outline the current state of immune checkpoint blockade drug development in HMs, and discuss mechanisms of activity and resistance, and highlight potential targets in the immune tumor microenvironment (TME)...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28529904/mini-review-of-conventional-and-hypofractionated-radiation-therapy-combined-with-immunotherapy-for-non-small-cell-lung-cancer
#10
REVIEW
Allison M Campbell, Roy H Decker
A successful antitumoral response requires immunological activation as well as an antigenic pool capable of stimulating both the innate and the adaptive immune system. Recent advances in immunotherapy have been aimed at boosting the activation status of the innate and adaptive immune system, including cytokine administration, monoclonal antibodies engineered to target high yield elements in oncogenic signaling pathways, cancer vaccines, and checkpoint inhibitors. Herein, we examine the ways that radiation therapy induced cell death provides a pool of stimulus antigen, and draw parallels from the immunobiology of autoimmunity to explore how the immunogenicity of antigen derived from radiation-induced cell death might augment the antitumoral response...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529903/immunotherapy-and-radiation-therapy-for-malignant-pleural-mesothelioma
#11
REVIEW
Evan W Alley, Sharyn I Katz, Keith A Cengel, Charles B Simone
Malignant pleural mesothelioma (MPM) is a particularly aggressive thoracic malignancy with limited survival following combination chemotherapy. As a result, there has been increased interested in immunotherapy for mesothelioma, both in the first-line and salvage settings. Early investigations of interleukin-2 (IL-2) and interferon alfa-2a/b have been limited by modest response rates and toxicity, whereas cytokine gene therapy is currently being investigated and shows early promise. The most prominent class of immunotherapies to be trialed with mesothelioma in the past half-decade has been immune checkpoint inhibitors (CPI)...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529902/current-state-of-immunotherapy-for-non-small-cell-lung-cancer
#12
REVIEW
Jyoti Malhotra, Salma K Jabbour, Joseph Aisner
Lung cancer is the leading cause of cancer mortality and non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancers. Platinum-based doublet chemotherapy is the standard first-line treatment for metastatic NSCLC when genomic testing reveals no targetable alteration such as epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) or ROS1 translocation/re-arrangements. But, chemotherapy produces response rates ranging only between 15-30%. For patients whose disease progresses on first-line chemotherapy, second-line therapy historically consists of taxane-based salvage chemotherapy with a response rate of less than 25%...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529900/immunotherapy-and-radiation-therapy-for-operable-early-stage-and-locally-advanced-non-small-cell-lung-cancer
#13
REVIEW
Neil K Taunk, Andreas Rimner, Melissa Culligan, Joseph S Friedberg, Julie Brahmer, Jamie Chaft
Non-small cell lung cancer (NSCLC) is the most common cause of cancer mortality. Although a significant proportion of patients can be cured with surgery, with or without adjuvant or neoadjuvant chemotherapy and radiation, a significant proportion of patients will fail, particularly distantly. Over fifty percent of patients present with stage IV disease. There are multiple forms of immunotherapy available including T-cell transfer, cytokine therapy, and oncolytic viruses. Checkpoint inhibitors have shown tremendous activity in NSCLC and are currently under intense study given promising data on response...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529899/clinical-experiences-of-combining-immunotherapy-and-radiation-therapy-in-non-small-cell-lung-cancer-lessons-from-melanoma
#14
REVIEW
Anusha Kalbasi, Ramesh Rengan
Radiation therapy (RT) is an essential component of local control for non-small cell lung cancer (NSCLC), but distant failures dictate the poor prognosis of this disease. Until recently, the possibility of using RT as an immunoadjuvant to stimulate a systemic anti-tumor immune response was not a realistic clinical opportunity. The emergence of immune checkpoint blockade as an effective immunotherapy for NSCLC has opened the door for combinatorial approaches involving RT. In melanoma, the body of preclinical evidence combining radiation and immunotherapy buoyed clinical efforts, from which promising results have begun to emerge...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529898/preclinical-rationale-for-combining-radiation-therapy-and-immunotherapy-beyond-checkpoint-inhibitors-i-e-cart
#15
REVIEW
James P Flynn, Mark H O'Hara, Saumil J Gandhi
An increasing appreciation for the role of the immune system in targeting cancer cells over the last decade has led to the development of several immunomodulatory agents aimed at enhancing the systemic antitumor immune response. One such method is the use of T cells that are genetically engineered to express chimeric antigen receptors (CARs). The remarkable success of this approach in advanced hematologic malignancies has garnered much enthusiasm for using this novel tool in treating other cancers. However, multiple challenges have hampered the application of this therapy to a broader set of solid tumors, most notably lung cancer...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529897/uncovering-the-immune-tumor-microenvironment-in-non-small-cell-lung-cancer-to-understand-response-rates-to-checkpoint-blockade-and-radiation
#16
REVIEW
Jonathan E Schoenhals, Steven N Seyedin, Clark Anderson, Eric D Brooks, Yun R Li, Ahmed I Younes, Sharareh Niknam, Ailin Li, Hampartsoum B Barsoumian, Maria Angelica Cortez, James W Welsh
The study of immunology has led to breakthroughs in treating non-small cell lung cancer (NSCLC). The recent approval of an anti-PD1 checkpoint drug for NSCLC has generated much interest in novel combination therapies that might provide further benefit for patients. However, a better understanding of which combinations may (or may not) work in NSCLC requires understanding the lung immune microenvironment under homeostatic conditions and the changes in that microenvironment in the setting of cancer progression and with radiotherapy...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529551/history-and-current-state-of-immunotherapy-in-glioma-and-brain-metastasis
#17
REVIEW
Tresa McGranahan, Gordon Li, Seema Nagpal
Malignant brain tumors such as glioblastoma (GBM) and brain metastasis have poor prognosis despite conventional therapies. Successful use of vaccines and checkpoint inhibitors in systemic malignancy has increased the hope that immune therapies could improve survival in patients with brain tumors. Manipulating the immune system to fight malignancy has a long history of both modest breakthroughs and pitfalls that should be considered when applying the current immunotherapy approaches to patients with brain tumors...
May 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28528510/immunogenomics-using-genomics-to-personalize-cancer-immunotherapy
#18
Rance C Siniard, Shuko Harada
While the use of genomic data has the potential to revolutionize patient care, there is still much work to be done with regard to the transformation of host-tumor interactions into favorable clinical outcomes for our patients. High-throughput technologies, such as next-generation sequencing (NGS), have rapidly advanced our understanding of oncology, and we are learning that most tumors do not simply possess consistently mutated genes that are responsible for tumorigenesis, facilitating the need for personalized cancer therapy...
May 20, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28527652/uveitis-induced-by-programmed-cell-death-protein-1-inhibitor-therapy-with-nivolumab-in-metastatic-melanoma-patient
#19
Hiroaki Kanno, Kyoko Ishida, Wataru Yamada, Takashi Nishida, Nobumichi Takahashi, Kiyofumi Mochizuki, Yuki Mizuno, Kanako Matsuyama, Tomoko Takahashi, Mariko Seishima
Nivolumab, a new immune checkpoint inhibitor, binds to programmed cell death-protein 1 receptors on T cell, blockades binding of its ligands, and augments the immunologic reaction against tumor cells. Augmented immune response, however, may lead to immune-related adverse events. Herein we describe a rare case of bilateral anterior uveitis induced by nivolumab treatment for metastatic melanoma. A 54-year-old woman presented with mild conjunctival redness and blurred vision two months after initiating nivolumab treatment...
May 17, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28525897/a-cellular-platform-for-the-evaluation-of-immune-checkpoint-molecules
#20
Sabrina Jutz, Annika Hennig, Wolfgang Paster, Ömer Asrak, Dejana Dijanovic, Florian Kellner, Winfried F Pickl, Johannes B Huppa, Judith Leitner, Peter Steinberger
Blockade of the T cell coinhibitory molecules CTLA-4 and PD-1 has clinical utility to strengthen T cell responses. In addition to these immune checkpoints an ever-growing number of molecules has been implicated in generating coinhibitory signals in T cells. However, investigating coinhibitory molecules in primary human cells is complicated by the restricted expression and promiscuity of both coinhibitory receptors and their ligands. Here we have evaluated the potential of fluorescence-based transcriptional reporters based on the human Jurkat T cell line in conjunction with engineered T cell stimulator cell lines for investigating coinhibitory pathways...
May 4, 2017: Oncotarget
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